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https://www.readbyqxmd.com/read/28339613/a-nonsense-mutation-in-ccdc62-gene-is-responsible-for-spermiogenesis-defects-and-male-infertility-in-repro29-repro29-mice%C3%A2
#1
Yuchi Li, Cailing Li, Shouren Lin, Bo Yang, Weiren Huang, Hanwei Wu, Yuanbin Chen, Lihua Yang, Manling Luo, Huan Guo, Jianbo Chen, Tiantian Wang, Qian Ma, Yanli Gu, Lisha Mou, Zhimao Jiang, Jun Xia, Yaoting Gui
Phenotype-driven mutagenesis is an unbiased method to identify novel genes involved in spermatogenesis and other reproductive processes. Male repro29/repro29 mice generated by the Reproductive Genomics Program at the Jackson Laboratory were infertile with deformed sperm and poor motility. Using selected exonic capture and massively parallel sequencing technologies, we identified a nonsense mutation in the exon 6 of coiled-coil domain-containing 62 gene (Ccdc62), which results in a formation of a premature stop codon and a truncated protein...
January 28, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28339541/vitamin-d-suppresses-oxidative-stress-induced-microparticle-release-by-human-umbilical-vein-endothelial-cells
#2
Xiuyue Jia, Jie Xu, Yang Gu, Xin Gu, Weimin Li, Yuping Wang
Endothelial microparticle (MP) release was increased in numerous cardiovascular diseases including preeclampsia. Oxidative stress is a potent inducer of endothelial dysfunction. In this study, we aimed to investigate if vitamin D could protect endothelial cells (ECs) from MP release induced by oxidative stress. Endothelial cell (from human umbilical vein) oxidative stress was induced by cultivation of cells under lowered oxygen condition (2%O2) for 48 h and cells cultured under standard condition (21%O2) served as control...
December 27, 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/28336771/dimerization-in-lbd16-and-lbd18-transcription-factors-is-critical-for-lateral-root-formation
#3
Han Woo Lee, Na Young Kang, Shashank Pandey, Chuloh Cho, Sung Haeng Lee, Jungmook Kim
LATERAL ORGAN BOUNDARIES (LOB) DOMAIN (LBD)/ASYMMETRIC LEAVES2-LIKE (ASL)s (hereafter referred to as LBD) are plant-specific transcription factors that play important roles in a plethora of plant growth and development. The leucine-zipper-like coiled-coil motif in the LOB domain of the class I LBD proteins has been proposed to mediate protein dimerization, but it has not been experimentally assessed yet. LBD16 and LBD18 have been well characterized to play important roles in lateral root development in Arabidopsis...
March 23, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28336437/overexpression-of-tacc3-is-correlated-with-tumor-aggressiveness-and-poor-prognosis-in-prostate-cancer
#4
Qiji Li, Liping Ye, Wei Guo, Min Wang, Shuai Huang, Xinsheng Peng
Transforming acidic coiled-coil (TACC3), a member of the TACC family, was previously reported to be deregulated in various cancers and identified to be involved in the tumor progression. However, its biological role and molecular mechanism in prostate cancer (PCa) have not been defined. Herein, we found that TACC3 was markedly upregulated in metastatic PCa. Upregulation of TACC3 was significantly associated with metastasis status, tumor stage, total PSA level, and Gleason score in PCa patients. Moreover, Kaplan-Meier survival analysis showed that PCa patients with high TACC3 had shorter disease-free survivals than those with low TACC3 expression...
March 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28327630/rassf-proteins-as-modulators-of-mst1-kinase-activity
#5
Aruna Bitra, Srinivas Sistla, Jessy Mariam, Harshada Malvi, Ruchi Anand
Rassf1A/5 tumor suppressors serve as adaptor proteins possessing a modular architecture with the C-terminal consisting of a coiled-coil SARAH (Salvador-Rassf-Hippo) domain and the central portion being composed of Ras associated (RA) domain. Here, we investigate the effect of Rassf effectors on Mst1 function by mapping the interaction of various domains of Rassf1A/5 and Mst1 kinase using surface plasmon resonance (SPR). The results revealed that apart from the C-terminal SARAH domain of Mst1 which interacts to form heterodimers with Rassf1A/5, the N-terminal kinase domain of Mst1 plays a crucial role in the stabilization of this complex...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325051/bioavailability-of-immobilized-epidermal-growth-factor-covalent-versus-noncovalent-grafting
#6
Nesrine Riahi, Frederic Murschel, Sophie Lerouge, Yves Durocher, Olivier Henry, Gregory De Crescenzo
In an effort to rationalize and optimize an antiapoptotic coating combining chondroitin sulfate (CS) and epidermal growth factor (EGF) for vascular applications, the authors here report the comparison of two grafting strategies aiming to display EGF in an oriented fashion on CS. For that purpose, the authors produced, purified, and characterized a chimeric protein corresponding to EGF that was N-terminally fused to a cysteine and a coil peptide. The chimera was covalently immobilized via its free thiol group or captured via coiled-coil interactions at the surface of a biosensor or on a chondroitin sulfate coating in multiwell plates, mimicking the coating that was previously developed by them for stent-graft surfaces...
March 21, 2017: Biointerphases
https://www.readbyqxmd.com/read/28322931/the-alternatively-spliced-lrrfip1-isoform-1-is-a-key-regulator-of-the-wnt-%C3%AE-catenin-transcription-pathway
#7
Pauline Labbé, Emilie Faure, Simon Lecointe, Solena Le Scouarnec, Florence Kyndt, Marie Marrec, Thierry Le Tourneau, Bernard Offmann, Cécile Duplaà, Stéphane Zaffran, Jean Jacques Schott, Jean Merot
The GC-rich Binding Factor 2/Leucine Rich Repeat in the Flightless 1 Interaction Protein 1 gene (GCF2/LRRFIP1) is predicted to be alternatively spliced in five different isoforms. Although important peptide sequence differences are expected to result from this alternative splicing, to date, only the gene transcription regulator properties of LRRFIP1-Iso5 were unveiled. Based on molecular, cellular and biochemical data, we show here that the five isoforms define two molecular entities with different expression profiles in human tissues, subcellular localizations, oligomerization properties and transcription enhancer properties of the canonical Wnt pathway...
March 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28320824/molecular-mechanism-of-dynein-recruitment-to-kinetochores-by-the-rod-zw10-zwilch-complex-and-spindly
#8
José B Gama, Cláudia Pereira, Patrícia A Simões, Ricardo Celestino, Rita M Reis, Daniel J Barbosa, Helena R Pires, Cátia Carvalho, João Amorim, Ana X Carvalho, Dhanya K Cheerambathur, Reto Gassmann
The molecular motor dynein concentrates at the kinetochore region of mitotic chromosomes in animals to accelerate spindle microtubule capture and to control spindle checkpoint signaling. In this study, we describe the molecular mechanism used by the Rod-Zw10-Zwilch complex and the adaptor Spindly to recruit dynein to kinetochores in Caenorhabditis elegans embryos and human cells. We show that Rod's N-terminal β-propeller and the associated Zwilch subunit bind Spindly's C-terminal domain, and we identify a specific Zwilch mutant that abrogates Spindly and dynein recruitment in vivo and Spindly binding to a Rod β-propeller-Zwilch complex in vitro...
March 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28319061/ccdc178-promotes-hepatocellular-carcinoma-metastasis-through-modulation-of-anoikis
#9
X Hu, Y Zhao, L Wei, B Zhu, D Song, J Wang, L Yu, J Wu
Hepatocellular carcinoma (HCC) is one of the most malignant tumors with high rate of recurrence and metastasis. Coiled-coil domain-containing protein 178 (CCDC178) has been reported to be mutated in HCC, whereas its role in physiological and pathologic process, including in human cancer, remains largely unknown. Here, we found that CCDC178 is upregulated in HCC tissues and its overexpression is correlated with pathological stage (P=0.003). CCDC178 deficiency reduced the anchorage-independent growth and anoikis resistance of HCC cells, and inhibited the HCC metastasis in vivo...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28318595/chchd10-mutations-in-patients-with-amyotrophic-lateral-sclerosis-in-mainland-china
#10
Shen Shen, Ji He, Lu Tang, Nan Zhang, Dongsheng Fan
Many genes have been found to be pathogenic for amyotrophic lateral sclerosis (ALS). Among them, the coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) has been reported to play a controversial role in ALS. We examined the coding region of this gene in 424 unrelated Chinese sporadic ALS subjects, 73 familial ALS subjects, and 204 healthy controls using a polymerase chain reaction-direct sequencing strategy. Two types of variants were identified, and of these, one variant (g.877C>T, p.P23L) was identified to be damaging, and the other one was (g...
February 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28316141/dasatinib-inhibits-actin-fiber-reorganization-and-promotes-endothelial-cell-permeability-through-rhoa-rock-pathway
#11
Swapan K Dasgupta, Anhquyen Le, K Vinod Vijayan, Perumal Thiagarajan
Treatment with dasatinib, a tyrosine kinase inhibitor, is associated with edema, pleural effusion, and pulmonary edema. We investigated the effect of dasatinib on the barrier function of human microvascular endothelial cells-1 (HMEC-1) in vitro and in vivo. The permeability of HMEC-1 to fluorescein isothiocyante (FITC)-dextran increased in Transwell chambers within 5 min following the addition of therapeutic concentrations of dasatinib. The change in permeability was associated with increased activation of RhoA GTPase and its effector Rho-associated coiled-coil kinase 1(ROCK1)...
March 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28304189/physiological-remodeling-of-bifurcation-aneurysms-preclinical-results-of-the-eclips-device
#12
Thomas R Marotta, Howard A Riina, Ian McDougall, Donald R Ricci, Monika Killer-Oberpfalzer
OBJECTIVE Intracranial bifurcation aneurysms are complex lesions for which current therapy, including simple coiling, balloon- or stent-assisted coiling, coil retention, or intrasaccular devices, is inadequate. Thromboembolic complications due to a large burden of intraluminal metal, impedance of access to side branches, and a high recurrence rate, due largely to the unmitigated high-pressure flow into the aneurysm (water hammer effect), are among the limitations imposed by current therapy. The authors describe herein a novel device, eCLIPs, and its use in a preclinical laboratory study that suggests the device's design and functional features may overcome many of these limitations...
March 17, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28299530/in-depth-characterization-of-the-homodimerization-domain-of-the-transcription-factor-thap1-and-dystonia-causing-mutations-therein
#13
Alev Richter, Ronja Hollstein, Eva Hebert, Franca Vulinovic, Juliane Eckhold, Alma Osmanovic, Reinhard Depping, Frank J Kaiser, Katja Lohmann
Mutations in the THAP1 gene encoding the transcription factor THAP1 have been shown to cause DYT6 dystonia. THAP1 contains a highly conserved THAP zinc finger at its N-terminal region which allows specific binding to its target sequences as well as a coiled-coil domain (amino acids 139-190) towards its C-terminus postulated as a protein-protein-binding motif. While several DYT6-causing mutations within the THAP domain were shown to decrease THAP1 activity in transcriptional regulation and DNA-binding, the role of mutations within the coiled-coil domain is rather unknown...
March 15, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28291748/the-crystal-structure-of-mouse-lc3b-in-complex-with-the-fyco1-lir-reveals-the-importance-of-the-flanking-region-of-the-lir-motif
#14
Shunya Sakurai, Taisuke Tomita, Toshiyuki Shimizu, Umeharu Ohto
FYVE and coiled-coil domain-containing protein 1 (FYCO1), a multidomain autophagy adaptor protein, mediates microtubule plus-end-directed autophagosome transport by interacting with kinesin motor proteins and with the autophagosomal membrane components microtubule-associated protein 1 light chain 3 (LC3), Rab7 and phosphatidylinositol 3-phosphate (PI3P). To establish the structural basis for the recognition of FYCO1 by LC3, the crystal structure of mouse LC3B in complex with the FYCO1 LC3-interacting region (LIR) motif peptide was determined...
March 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28289084/control-of-recombination-directionality-by-the-listeria-phage-a118-protein-gp44-and-the-coiled-coil-motif-of-its-serine-integrase
#15
Sridhar Mandali, Kushol Gupta, Anthony R Dawson, Gregory D Van Duyne, Reid C Johnson
The serine integrase of phage A118 catalyzes integrative recombination between attP on the phage and a specific attB locus on the chromosome of Listeriamonocytogenes but is unable to promote excisive recombination between the hybrid attL and attR sites found on the integrated prophage without assistance from a Recombination Directionality Factor (RDF). We have identified and characterized the phage-encoded RDF, Gp44, which activates the A118 integrase for excision and inhibits integration. Gp44 binds to the C-terminal DNA binding domain of integrase, and we have localized the primary binding site to be within the mobile coiled-coil (CC) motif but distinct from the distal tip of the CC that is required for recombination...
March 13, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28287465/serine-threonine-kinase-3-phosphoinositide-dependent-protein-kinase-1-pdk1-as-a-key-regulator-of-cell-migration-and-cancer-dissemination
#16
REVIEW
Laura Di Blasio, Paolo A Gagliardi, Alberto Puliafito, Luca Primo
Dissecting the cellular signaling that governs the motility of eukaryotic cells is one of the fundamental tasks of modern cell biology, not only because of the large number of physiological processes in which cell migration is crucial, but even more so because of the pathological ones, in particular tumor invasion and metastasis. Cell migration requires the coordination of at least four major processes: polarization of intracellular signaling, regulation of the actin cytoskeleton and membrane extension, focal adhesion and integrin signaling and contractile forces generation and rear retraction...
March 11, 2017: Cancers
https://www.readbyqxmd.com/read/28286005/overall-shapes-of-the-smc-scpab-complex-are-determined-by-balance-between-constraint-and-relaxation-of-its-structural-parts
#17
Katsuhiko Kamada, Masayuki Su'etsugu, Hiraku Takada, Makoto Miyata, Tatsuya Hirano
The SMC-ScpAB complex plays a crucial role in chromosome organization and segregation in many bacteria. It is composed of a V-shaped SMC dimer and an ScpAB subcomplex that bridges the two Structural Maintenance of Chromosomes (SMC) head domains. Despite its functional significance, the mechanistic details of SMC-ScpAB remain obscure. Here we provide evidence that ATP-dependent head-head engagement induces a lever movement of the SMC neck region, which might help to separate juxtaposed coiled-coil arms. Binding of the ScpA N-terminal domain (NTD) to the SMC neck region is negatively regulated by the ScpB C-terminal domain...
March 7, 2017: Structure
https://www.readbyqxmd.com/read/28283191/ccdc181-is-a-microtubule-binding-protein-that-interacts-with-hook1-in-haploid-male-germ-cells-and-localizes-to-the-sperm-tail-and-motile-cilia
#18
Thomas Schwarz, Barbara Prieler, Johannes A Schmid, Pawel Grzmil, Juergen Neesen
Disruption of murine Hook1 results in a disturbed spermatogenesis and consequently leads to male infertility in mice. Within these mice abnormal sperm development starts with a disorganization of the microtubular manchette in elongating spermatids that leads to an abnormal head shape as well as to distinctive structural changes in the flagella of the sperm. To elucidate Hook1 function in male germ cell differentiation a yeast two-hybrid screen was performed using a murine testicular library, which leads to the identification of several putative Hook1 interacting proteins...
February 20, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28275738/long-range-allosteric-signaling-in-red-light-regulated-diguanylyl-cyclases
#19
Geoffrey Gourinchas, Stefan Etzl, Christoph Göbl, Uršula Vide, Tobias Madl, Andreas Winkler
Nature has evolved an astonishingly modular architecture of covalently linked protein domains with diverse functionalities to enable complex cellular networks that are critical for cell survival. The coupling of sensory modules with enzymatic effectors allows direct allosteric regulation of cellular signaling molecules in response to diverse stimuli. We present molecular details of red light-sensing bacteriophytochromes linked to cyclic dimeric guanosine monophosphate-producing diguanylyl cyclases. Elucidation of the first crystal structure of a full-length phytochrome with its enzymatic effector, in combination with the characterization of light-induced changes in conformational dynamics, reveals how allosteric light regulation is fine-tuned by the architecture and composition of the coiled-coil sensor-effector linker and also the central helical spine...
March 2017: Science Advances
https://www.readbyqxmd.com/read/28273854/overexpression-of-transforming-acidic-coiled-coil%C3%A2-containing-protein-3-reflects-malignant-characteristics-and-poor-prognosis-of-glioma
#20
Ying Sun, Yu Tian, Guang-Zhi Wang, Shi-Hong Zhao, Bo Han, Yong-Li Li, Chuan-Lu Jiang
Gliomas are malignant primary brain tumors with poor prognosis. Recently, research was indicative of a tight connection between tumor malignancy and genetic alterations. Here, we propose an oncogenic implication of transforming acidic coiled-coil-containing protein 3 (TACC3) in gliomas. By comprehensively analyzing the Chinese glioma genome atlas (CGGA) and publicly available data, we demonstrated that TACC3 were overexpressed along with glioma grade and served as an independent negative prognostic biomarker for glioma patients...
March 4, 2017: International Journal of Molecular Sciences
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